Proteolytic enzymes have many physiological functions, ranging from generalized protein digestion to specifically regulated processes such as the activation of zymogens, blood coagulation, the lysis of blood clots, and the release of blood pressure regulating peptides from precursor proteins. Specific enzyme inhibitors are normally used as biochemical tools in the analysis of biological functions. However, the exact role of many proteolytic enzymes in such physiological processes has been difficult to determine because of a current lack of specific enzyme inhibitors. The synthesis of peptide inhibitors of trypsin-like serine and thiol proteinases, which are based on the structure of the natural proteinase inhibitor, leupeptin, is proposed. We will evaluate the biological effects of the synthetic analogs using appropriate esterase and proteinase assays. This will allow for a rapid determination of the effectiveness of the inhibitors synthesized, and the value of the changes made in the inhibitor structure. In an effort to gain information leading to the enhancement of the selectivity and potency of inhibitors structure-activity and structure-selectivity correlations will be drawn for the synthetic inhibitors. This project was designed as a research effort which will allow undergraduate students training in organic synthesis, instrumental techniques, biochemical analysis, and statistical treatment of data in addition to other research training not normally available at this stage in their education, through an enhancement of the research environment at this undergraduate institution.